Exploiting synthetic lethal interactions between DNA damage signaling, checkpoint control, and p53 for targeted cancer therapy

Abstract

DNA damage signaling and checkpoint control pathways are among the most commonly mutated networks in human tumors. Emerging data suggest that synthetic lethal interactions between mutated oncogenes or tumor suppressor genes with molecules involved in the DNA damage response and DNA repair pathways can be therapeutically exploited to preferentially kill cancer cells. In this review, we discuss the concept of synthetic lethality with a focus on p53, a commonly lost tumor suppressor gene, in the context of DNA damage signaling. We describe several recent examples in which this concept was successfully applied to target tumor cells in culture or in mouse models, as well as in human cancer patients.